The macronuclear DNA of the protozoan, Oxytricha, exists naturally as small, genesized pieces rather than as long chromosomal molecules. These DNA pieces arise through the degradation of DNA in a micronucleus, accompanied by the elimination of more than 90% of the micronuclear DNA complexity. By studying individual macronuclear DNA molecules, we hope to gain information on gene structure and activity. As a first step, we have been examining the genes for rRNA. The rDNA is a linear molecule 6,700 base pairs long. Of these, about 600 base pairs are a non-transcribed region adjacent to the site of initiation of rRNA transcription and are likely to be involved with control of rRNA synthesis. We will examine this region by molecular hybridization and nucleotide sequencing. We are also looking for possible terminal repeated sequences which may be related to rDNA replication or rDNA processing. Other macronuclear sequences have been isolated by molecular cloning. With these we are also testing for non-transcribed regions, terminal repeats and possible gene insertions. A separate but related series of experiments will examine the relationship of the organization of DNA sequences in the micronucleus to the same sequences in the macronucleus, concentrating on changes due to DNA processing and on chromosomal sequences adjacent to genes. With these experiments we hope to learn more about the structure of genetic units and the arrangement of genes in the chromosome.